Buxton P G, Kostakopoulou K, Brickell P, Thorogood P, Ferretti P
Developmental Biology Unit, Institute of Child Health, University College London, United Kingdom.
Int J Dev Biol. 1997 Aug;41(4):559-68.
The slug gene encodes a zinc finger transcription factor expressed by neural crest cells (Nieto et al., Science 264: 835-839, 1994) and by certain non-crest derived mesenchymal cell populations, such as lateral mesoderm and sclerotome (Mayor et al., Development 121: 767-777, 1995; Buxton et al., Dev. Biol. 183: 150-165, 1997). We report here that slug is also expressed in developing chick limbs. The slug expression domain in the limb bud expands from posterior to anterior and marks cells that are predominantly destined to become chondrocytes but have not yet differentiated. Its expression is maintained in connective tissue, but is never observed in the premuscle masses. We show that removal of the apical ectodermal ridge results in loss of slug expression which can be arrested by the addition of an FGF-4 bead. Retinoic acid bead implants lead to down-regulation of slug expression, again accompanied by abolition of limb outgrowth. Dual bead implants demonstrate antagonism between these two factors, suggesting that a localized antagonistic effect between endogenous RA and FGF-4 on slug expression underlies the molecular mechanism controlling the transition between undifferentiated and differentiated state during normal limb development. The fact that slug expression pattern correlates with areas of growth in the limb, and is maintained by FGF-4 and down-regulated by retinoic acid, indicates that slug-expressing cells play a crucial role in growth and patterning of the chick limb. We propose that slug expression provides the best correlation to date between a molecular marker and the physical concept of the progress zone, defined as "a labile region where new positional values are successively engendered in the course of growth" (Summerbell et al., Nature 244: 492-496, 1973).
蛞蝓基因编码一种锌指转录因子，该因子由神经嵴细胞表达（涅托等人，《科学》264: 835 - 839，1994年），也由某些非嵴衍生的间充质细胞群体表达，如外侧中胚层和生骨节（马约尔等人，《发育》121: 767 - 777，1995年；巴克斯顿等人，《发育生物学》183: 150 - 165，1997年）。我们在此报告，蛞蝓基因在发育中的鸡胚肢体中也有表达。肢体芽中蛞蝓基因的表达区域从后向前扩展，标记的细胞主要注定会成为软骨细胞但尚未分化。其表达在结缔组织中维持，但在肌前体团块中从未观察到。我们表明，去除顶端外胚层嵴会导致蛞蝓基因表达丧失，而添加FGF - 4珠可阻止这种丧失。视黄酸珠植入导致蛞蝓基因表达下调，同样伴随着肢体生长的停止。双珠植入证明了这两种因子之间的拮抗作用，表明内源性视黄酸和FGF - 4对蛞蝓基因表达的局部拮抗作用是正常肢体发育过程中控制未分化状态和分化状态转变的分子机制基础。蛞蝓基因表达模式与肢体生长区域相关，并由FGF - 4维持且被视黄酸下调这一事实表明，表达蛞蝓基因的细胞在鸡胚肢体的生长和模式形成中起关键作用。我们提出，蛞蝓基因表达与“进展区”这一物理概念之间提供了迄今为止最佳的相关性，进展区被定义为“在生长过程中连续产生新位置值的不稳定区域”（萨默贝尔等人，《自然》244: 492 - 496，1973年）。
